P632: ORAL AND GUT MICROBIAL DIVERSITY CORRELATES WITH PROGNOSTIC FEATURES IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: M. Szelest, M. Paziewska, M. Kiełbus, M. Masternak, J. Zaleska, E. Wawrzyniak, E. Kalicińska, P. Jabłonowska, T. Wróbel, A. Wolska-Washer, J. Z. Błoński, K. Giannopoulos
Journal: HemaSphere (2022)

Background: For the last years it has been speculated that immunologic and inflammatory factors, including antigen stimulation, could be involved in the pathogenesis of chronic lymphocytic leukemia (CLL). With increasing evidence that the activation of cellular proinflammatory signaling pathways driven by somatic mutations and an increased release of proinflammatory cytokines is associated with CLL development, it seems relevant to investigate the role of chronic inflammation in the pathogenesis of this disease. Recent studies have revealed that the intestinal microbiota could modulate the activity of immune system through creating an imbalance between cell proliferation and apoptosis. Thus, the relationship of microbial dysbiosis and specific taxon abundances with CLL biology and clinical outcome should be examined. Aims: As it was reported that the activity of human microbiome is involved in cancer development and host response against anticancer therapy, the aim of this study was to investigate the stool and oral microbiome alterations in CLL patients with respect to selected prognostic and predictive markers. Methods: The study included 92 patients with untreated CLL. Microbiota composition of 85 stool samples and 76 oral samples from these cases were determined by 16S rRNA next-generation sequencing and analyzed with respect to the Binet stage, IGHV and TP53 mutation status, CD38 and ZAP-70 expression, and cytogenetic aberrations. The species richness and evenness were analyzed using Shannon and Chao1 indexes, respectively. The DADA2 tool was used to classify sequences into appropriate taxonomic groups. The differences in taxonomic profiles and species diversity in oral and stool samples with distinct prognostic features were investigated using the Wilcoxon or Kruskall-Wallis tests. Results: Alpha-diversity analysis indicates that there were no significant differences in richness and evenness between probes with distinct CLL features in both fecal and oral samples. However, at phylum level, an increase in Proteobacteria, a common feature of gut dysbiosis, was observed in stool samples from patients with stage Binet C compared to stage Binet A (p=0.042), and in oral samples with del11q compared to samples with no del11q (p=0.021). The abundance of Bacteroidota was higher in fecal samples collected from patients with stage Binet A in comparison to stage Binet B (p=0.051) and C (p=0.009). Moreover, Bacteroidota was relatively more abundant in oral samples from patients with stage Binet A in comparison to stage Binet C (p=0.008). Bacteroidota was significantly less abundant in stool samples from patients with unmutated IGHV compared to samples with mutated IGHV (p=0.029). Stool samples from patients with CD38+ exhibited decreased abundance of Bacteroidota and increased abundance of Firmicutes in comparison to CD38- cases (p=0.031 and p=0.022, respectively). Furthermore, fecal samples from patients with del6q showed a higher abundance of Firmicutes and lower abundance of Bacteroidota compared to samples with no del6q (p=0.006 and p=0.018, respectively). Additionally, a relative increase in Actinobacteriota and Firmicutes was found in oral samples with tri12 in comparison to samples with no tri12 (p=0.039 and p=0.016, respectively). Image:Summary/Conclusion: Our findings provide new insights into oral and gut microbial diversity which is related to distinct prognostic features in CLL and might point to the inflammatory-related modulation of the clinical course of disease.